Psychological and behavioral states are known to exert a profound impact on the immune system, and can delay the onset of acute inflammation and healing of injured tissues. Previous research from our group and others has shown that psychological influences on immune functions can be highly subtle and diverse. Personality factors, attitudes and beliefs can lead to a down-regulation of immune function, and likely do so by an overlapping set of common mechanisms. While animal models may not approximate the intricacies of human psychology, they afford an important and necessary approach to understanding the mechanistic links between psychological states and health outcomes. Other projects of this proposal focus on healing of peripheral wounds, but from the vantage of psychological processes, a highly relevant issue is the impact of behavioral states on healing of brain injuries. After spinal cord injury, repair and regeneration of damaged tissues, both CNS and peripheral, is dependent on inflammatory processes. Life expectancy of spinal injured individuals has increased to a level that is consistent with the able bodied population. SCI survivors must learn to cope with the psychological stress of disability as well as the physiological challenges of rehabilitation, and these latter factors likely impact on recovery. In the present proposal, we will address the interrelationship between psychological stress, and wound healing in a clinically relevant model of SCI. A major hypothesis of this proposal is that physiological and psychological factors associated with SCI, and damage to sympathetic outflow will suppress inflammatory processes resulting in slowed or incomplete wound healing of both CNS and peripheral tissues. We will identify the time course of hypothalamic- pituitary-adrenal and sympathetic-adrenal medullary activation after SCI injuries in mice, which can then be correlated with measures of acute inflammation in wounds of the skin and spinal cord. Morphometric analysis of immunohistochemically-stained skin (above and below the level of SCI) and injured spinal cord sections will allow us to determine how altered immunological processes affect wound healing in the periphery and CNS. The addition of a psychological stressor (restraint stress), will further illuminate how stress may impact on wound healing and inflammation, especially under conditions where the immune system and CNS are uncoupled, as in spinal injury.